Tumor microenvironment shows an immunological abscopal effect in patients with NSCLC treated with pembrolizumab-radiotherapy combination.

Autor:	van der Woude LL; Department of Tumour Immunology, Radboudumc, Nijmegen, The Netherlands.; Department of Pathology, Radboudumc, Nijmegen, The Netherlands.; Division of Immunotherapy, Oncode Institute, Radboudumc, Nijmegen, the Netherlands., Gorris MAJ; Department of Tumour Immunology, Radboudumc, Nijmegen, The Netherlands.; Division of Immunotherapy, Oncode Institute, Radboudumc, Nijmegen, the Netherlands., Wortel IMN; Data Science, Institute for Computing and Information Sciences, Radboud University, Nijmegen, the Netherlands., Creemers JHA; Department of Tumour Immunology, Radboudumc, Nijmegen, The Netherlands.; Division of Immunotherapy, Oncode Institute, Radboudumc, Nijmegen, the Netherlands., Verrijp K; Department of Tumour Immunology, Radboudumc, Nijmegen, The Netherlands.; Department of Pathology, Radboudumc, Nijmegen, The Netherlands.; Division of Immunotherapy, Oncode Institute, Radboudumc, Nijmegen, the Netherlands., Monkhorst K; Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Grünberg K; Department of Pathology, Radboudumc, Nijmegen, The Netherlands., van den Heuvel MM; Department of Pulmonary Diseases, Radboudumc, Nijmegen, The Netherlands., Textor J; Department of Tumour Immunology, Radboudumc, Nijmegen, The Netherlands.; Data Science, Institute for Computing and Information Sciences, Radboud University, Nijmegen, the Netherlands., Figdor CG; Department of Tumour Immunology, Radboudumc, Nijmegen, The Netherlands., Piet B; Department of Pulmonary Diseases, Radboudumc, Nijmegen, The Netherlands., Theelen WSME; Department of Pulmonology, Netherlands Cancer Institute, Amsterdam, The Netherlands., de Vries IJM; Department of Tumour Immunology, Radboudumc, Nijmegen, The Netherlands jolanda.devries@radboudumc.nl.
Jazyk:	angličtina
Zdroj:	Journal for immunotherapy of cancer [J Immunother Cancer] 2022 Oct; Vol. 10 (10).
DOI:	10.1136/jitc-2022-005248
Abstrakt:	Background: Immunotherapy is currently part of the standard of care for patients with advanced-stage non-small cell lung cancer (NSCLC). However, many patients do not respond to this treatment, therefore combination strategies are being explored to increase clinical benefit. The PEMBRO-RT trial combined the therapeutic programmed cell death 1 (PD-1) antibody pembrolizumab with stereotactic body radiation therapy (SBRT) to increase the overall response rate and study the effects on the tumor microenvironment (TME). Methods: Here, immune infiltrates in the TME of patients included in the PEMBRO-RT trial were investigated. Tumor biopsies of patients treated with pembrolizumab alone or combined with SBRT (a biopsy of the non-irradiated site) at baseline and during treatment were stained with multiplex immunofluorescence for CD3, CD8, CD20, CD103 and FoxP3 for lymphocytes, pan-cytokeratin for tumors, and HLA-ABC expression was determined. Results: The total number of lymphocytes increased significantly after 6 weeks of treatment in the anti-PD-1 group (fold change: 1.87, 95% CI: 1.06 to 3.29) and the anti-PD-1+SBRT group (fold change: 2.29, 95% CI: 1.46 to 3.60). The combination of SBRT and anti-PD-1 induced a 4.87-fold increase (95% CI: 2.45 to 9.68) in CD103 + cytotoxic T-cells 6 weeks on treatment and a 2.56-fold increase (95% CI: 1.03 to 6.36) after anti-PD-1 therapy alone. Responders had a significantly higher number of lymphocytes at baseline than non-responders (fold difference 1.85, 95% CI: 1.04 to 3.29 for anti-PD-1 and fold change 1.93, 95% CI: 1.08 to 3.44 for anti-PD-1+SBRT). Conclusion: This explorative study shows that that lymphocyte infiltration in general, instead of the infiltration of a specific lymphocyte subset, is associated with response to therapy in patients with NSCLC.Furthermore, anti-PD-1+SBRT combination therapy induces an immunological abscopal effect in the TME represented by a superior infiltration of cytotoxic T cells as compared with anti-PD-1 monotherapy. Competing Interests: Competing interests: WSMET reports grants from AstraZeneca, MSD and Sanofi. (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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